Immunologically mediated renal disease constitutes a major cause of renal failure in man. The objective of the proposed research is to gain new insights into the pathogenesis of renal disease mediated by immunologic mechanisms through a comprehensive immunopathologic study of: the role of glomerular factors on the localization and clearance of immune complexes in the glomerular capillary wall and the glomerular mesangium, the effects of immunologic and chemical alterations of the glomerulus and of other macromolecules within the mesangium on the mesangial uptake and transport of macromolecules, and of the factors influencing and the consequences of tubular immune complex formation and clearance through studies of the kinetics of immune tubular injury mediated by antibodies to Tamm-Horsfall protein. These studies will be performed in rats, rabbits, gerbils, mice and guinea pigs. The methods employed will include renal transplantation and renal perfusion in rats, and quantitative macromolecular tracer, biochemical radioistope, immunologic and immunopathologic techniques.